Fasting glucose variability in young adulthood and incident diabetes, cardiovascular disease and all-cause mortality
The aim of this study was to determine whether long-term intra-individual variability in fasting glucose (FG) during young adulthood is associated with incident diabetes, cardiovascular disease (CVD) and mortality.
We included participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study, ages 18–30 years at baseline (1985–1986) and followed with eight examinations for up to 30 years. Long-term glucose variability was assessed using the CV (CV-FG) and the absolute difference between successive FG measurements (average real variability; ARV-FG). For participants who developed any event (diabetes, CVD or mortality), FG variability measurement was censored at the examination prior to event ascertainment. We estimated HRs for incident diabetes, CVD and mortality with adjustment for demographics, baseline FG, change in FG (censor – baseline) and time-varying education, smoking, alcohol consumption, BMI, physical activity, systolic BP, BP medications, LDL-cholesterol and cholesterol medications (and incident diabetes and diabetes medications for CVD and mortality outcomes).
Among 3769 black and white participants, there were 317 incident diabetes cases (102,677 person-years), 159 incident CVD events (110,314 person-years) and 174 deaths (111,390 person-years). After adjustment, HRs per 1 SD higher ARV-FG were 1.64 (95% CI 1.52, 1.78) for diabetes, 1.15 (95% CI 1.01, 1.31) for CVD and 1.25 (95% CI 1.11, 1.40) for mortality. The HRs per 1 SD higher CV-FG were 1.39 (95% CI 1.21, 1.58) for diabetes, 1.32 (95% CI 1.13, 1.54) for CVD and 1.08 (95% CI 0.92, 1.27) for mortality, after adjustment. The cause-specific HRs per 1 SD higher ARV-FG were 1.29 (95% CI 1.14, 1.47) for non-CVD death and 1.05 (95% CI 0.76, 1.45) for CVD death. We did not observe evidence for effect modification of any association by sex or race.
Our results suggest that higher intra-individual FG variability during young adulthood before the onset of diabetes is associated with incident diabetes, CVD and mortality.
KeywordsCardiovascular disease Epidemiology Fasting blood glucose Glucose variability Mortality Type 2 diabetes Young adulthood
Average real variability
Average real variability of fasting glucose
Coronary Artery Risk Development in Young Adults
CV of fasting glucose
The authors thank the other investigators, the staff and the participants of the CARDIA study for their valuable contributions.
MPB is the guarantor of this work, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. MPB and MRC conceptualised the study and designed the analysis plan. MPB performed all statistical analyses and drafted the manuscript. MRC provided supervision to MPB. All coauthors, MPB, APC, CEL, EPG, JPR, PJS, YY and MRC, contributed to the acquisition, analysis or interpretation of data; provided critical revision of the manuscript for important intellectual content and contributed to the discussion; and approve the final version of this manuscript.
MPB was partially supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health under Award Number T32HL069771 to conduct the current work. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the NHLBI in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), the University of Minnesota (HHSN268201800006I) and the Kaiser Foundation Research Institute (HHSN268201800004I). The ancillary study to CARDIA (R01 DK106201, EPG, Principal Investigator) from the National Institute of Diabetes, Digestive and Kidney Diseases supported data collection for this study. The funders/sponsor of this study had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; or the decision to submit the manuscript for publication.
Duality of interest
EPG receives funding unrelated to the current study from Janssen Pharmaceuticals, Inc. (June 2017). APC receives research funding unrelated to the current study from Amgen, Inc. The remaining authors declare that there is no duality of interest associated with this manuscript. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the NHLBI, the National Institutes of Health or the US Department of Health and Human Services.
- 3.Hirakawa Y, Arima H, Zoungas S et al (2014) Impact of visit-to-visit glycemic variability on the risks of macrovascular and microvascular events and all-cause mortality in type 2 diabetes: the ADVANCE trial. Diabetes Care 37(8):2359–2365. https://doi.org/10.2337/dc14-0199 CrossRefPubMedGoogle Scholar
- 8.Wang A, Liu X, Xu J et al (2017) Visit-to-visit variability of fasting plasma glucose and the risk of cardiovascular disease and all-cause mortality in the general population. J Am Heart Assoc 6(12):e006757. https://doi.org/10.1161/JAHA.117.006757
- 10.Cardoso CRL, Leite NC, Moram CBM, Salles GF (2018) Long-term visit-to-visit glycemic variability as predictor of micro- and macrovascular complications in patients with type 2 diabetes: The Rio de Janeiro Type 2 Diabetes Cohort Study. Cardiovasc Diabetol 17(1):33. https://doi.org/10.1186/s12933-018-0677-0 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Mendez CE, Mok KT, Ata A, Tanenberg RJ, Calles-Escandon J, Umpierrez GE (2013) Increased glycemic variability is independently associated with length of stay and mortality in noncritically ill hospitalized patients. Diabetes Care 36(12):4091–4097. https://doi.org/10.2337/dc12-2430 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.American College of Sports Medicine (1993) The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness in healthy adults. Position stand of the American College of Sports Medicine. Schweiz Z Sportmed 41:127–137Google Scholar
- 18.Hozawa A, Jacobs DR Jr, Steffes MW, Gross MD, Steffen LM, Lee DH (2009) Circulating carotenoid concentrations and incident hypertension: the Coronary Artery Risk Development in Young Adults (CARDIA) study. J Hypertens 27(2):237–242. https://doi.org/10.1097/HJH.0b013e32832258c9 CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Bancks MP, Kershaw K, Carson AP, Gordon-Larsen P, Schreiner PJ, Carnethon MR (2017) Association of modifiable risk factors in young adulthood with racial disparity in incident type 2 diabetes during middle adulthood. JAMA 318(24):2457–2465. https://doi.org/10.1001/jama.2017.19546 CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Yano Y, Ning H, Allen N et al (2014) Long-term blood pressure variability throughout young adulthood and cognitive function in midlife: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Hypertension 64(5):983–988. https://doi.org/10.1161/HYPERTENSIONAHA.114.03978 CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Yuan YC (2000) Multiple Imputation for missing data: concepts and new development (version 9.0). In: Proceedings of the Twenty-Fifth Annual SAS Users Group International Conference. SAS Institute, Cary, NC, pp 1–11Google Scholar